title: Enhanced G2 chromatid radiosensitivity in dyskeratosis congenita fibroblasts.
abstract: Dyskeratosis congenita (DC) is an inherited disorder characterized by reticular pigmentation of the skin, dystrophic nails, mucosal leukoplakia, and a predisposition to cancer in early adult life. In the majority of cases, DC is an X-linked recessive trait. However, one or more autosomal form(s) of DC may exist. Although excessive spontaneous chromatid breakage has been reported in DC, it is not a consistent cytological marker for this disorder. We examined the frequency and specificity of X-irradiation-induced G2 chromatid breakage in fibroblasts from three unrelated DC patients (two males and one female). Metaphase cells from DC patients had significantly more chromatid breaks (16-18-fold and 17-26-fold at 50 and 100 rad X-irradiation, respectively) and chromatid gaps (10-12-fold and 6-7-fold at 50 and 100 rad, respectively) than those from two different controls. Analysis of banded chromosomes revealed a nonrandom distribution of chromatid aberrations in DC but not in controls, a distribution corresponding to some of the known breakpoints for cancer-specific rearrangements, constitutive fragile sites, and/or loci for cellular proto-oncogenes. The significance of this finding for cancer predisposition in DC patients is uncertain, but the increased susceptibility of X-irradiation-induced chromatid breakage may serve as a cellular marker of diagnostic value.
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston 29425.
authors.forename: D M
authors.initials: DM
authors.lastname: DeBauche
authors.forename: G S
authors.initials: GS
authors.lastname: Pai
authors.forename: W S
authors.initials: WS
authors.lastname: Stanley
mesh_terms: D002460:Cell Line; D002842:Chromatids / Q000528:radiation effects*; D002869:Chromosome Aberrations; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D005260:Female; D005347:Fibroblasts / Q000528:radiation effects; D006801:Humans; D007399:Interphase; D008297:Male; D008677:Metaphase; D010859:Pigmentation Disorders / Q000151:congenital / Q000235:genetics*; D014965:X-Rays